Taxing Cannabis

Cannabis

Cannabis/Cannabinoids & Depression

Introduction & History

Depression is a term used to describe a variety of different disorders characterised by lowering of mood, disinterest in ones surroundings or condition, fatigue, and loss of appetite and/or personal neglect.

For most people, depression is a passing mood, for others it is a debilitating condition with severe emotional and physical symptoms. Only when depression is serious is it normally considered a psychiatric disorder requiring treatment. Most drug treatments for clinical depression involve use of tricyclic antidepressants (e.g. amitriptyline), monoamine oxidase inhibitors (e.g. isocarboxazid) or more recently fluotexine (prozac), both of which boost levels of brain catecholamines (stimulant neurotransmitters including noradrenalin or serotonin).

Cannabis products have long been considered to be effective in the treatment of depressive disorders, in 1845 it was recommended for melancholia (with obsessive rumination) and mental disorder in general[i]. In 1947 Stockings[ii] found improvements in 36 out of 50 depressed mental patients treated with a synthetic cannabinoid.

On the opposing side, cannabis has long been accused of causing an amotivational syndrome whereby the user withdraws from society and is unable to function normally. The apathy and lack of engagement associated with the amotivational syndrome has given way to depression as a significant health concern in relation to cannabis use.

For this report a Medline search using keywords cannabi* and depression identified a total of 1016 scientific papers, this review concentrates on human studies.

Case Studies showing links between cannabis use and depression

In a case study Bolls[iii] reported a case of post-natal depression successfully treated by a large oral dose (4g of alcoholic cannabis tincture) and counselling. The subject reported anxiety at the peak of the drugs effect, however the study involved a single case, was not controlled under current scientific methodology, and it could not now be concluded whether any recovery was due to the drug, the psychotherapy, or would have occurred in any event. Conversely Payne[iv] reported a case history where cannabis use was considered to worsen the patient’s mood disorder. In a case study of a brain-damaged patient, Payne[v] noted “The impact of cannabis use in this individual appeared to have a detrimental effect on his mood.”

Population Studies

In a large scale population study of 85000 subjects from 17x countries investigating the link between early-onset cannabis use and later-onset depression, de Graaf et al[vi] found “The overall association was modest (controlled for sex and age, risk ratio = 1.5, 95% confidence interval: 1.4, 1.7), was statistically robust in 5 countries, and showed no sex difference.”

Scott et al[vii] reported that in Australian adolescents “Hallucinations were associated with depressive disorder (OR 2.70; 95% CI 1.16, 6.28) and were more prevalent in those adolescents who had smoked cannabis more than twice in the month prior to the survey (OR 3.27; 95% CI 1.76, 6.08)” In a study of young adults, cannabis use and depression, Harder et al[viii] concluded “The evidence does not support a causal association linking adolescent-onset cannabis problems with young adult depression.” In Australian aborigines, Lee et al[ix] reported “After adjusting for other substance use (tobacco, alcohol and lifetime petrol sniffing), age and sex, heavy cannabis users were four times more likely than the remainder of the sample to report moderate to severe depressive symptoms (odds ratio, 4.1; 95% CI, 1.3-13.4).”

In a community cohort of young adults, Leventhal et al[x] found “cannabis use disorders were not robustly associated with melancholia” Beck et al[xi] noted “Students with higher levels of depressive symptoms were more likely to use cannabis in an emotional pain or sex-seeking context.”

In Dutch schoolchildren, Monshouwer et al[xii] reported “cannabis use was linked to externalising problems (delinquent and aggressive behaviour) but not to internalising problems (withdrawn behaviour, somatic complaints and depression).” Medina et al[xiii] reported “Marijuana use and white matter volume were additive and interactive in predicting depressive symptoms among adolescents.” In Italian students, Innamorati et al[xiv] noted “a widespread use of cannabis among students and its association with risky behaviors, anxiety and depression, and suicide risk.”

In a study of patients with depression, Roeffels et al[xv] reported “Cannabis use (11%) was associated with younger age, male gender, single marital status, white ethnicity, less education, recurrent depression, agoraphobia, and hazardous alcohol use.” Buckner et al[xvi] reported “Consistent with other reports, depression was correlated with alcohol and cannabis problems. As predicated, distress tolerance mediated the relationships between depression and alcohol and cannabis problems.”

Heavy and/or Dependent Cannabis Users

In a study of patients seeking treatment for cannabis dependence, Guillem et al[xvii] found 38% to have reported major depressive disorder within the previous 12 months. Studying cannabis withdrawal symptoms, Cornelius et al[xviii] found “the most common withdrawal symptoms among those with cannabis dependence were craving (82%), irritability (76%), restlessness (58%), anxiety (55%), and depression (52%).”

Based on an internet survey, Looby & Earlywine[xix] found daily cannabis users meeting dependence criteria were significantly more likely to report problems with depression than non-dependent daily users From an internet survey Denson & Earlywine[xx] reported “Despite comparable ranges of scores on all depression subscales, those who used once per week or less had less depressed mood, more positive affect, and fewer somatic complaints than non-users. Daily users reported less depressed mood and more positive affect than non-users. The three groups did not differ on interpersonal symptoms. Separate analyses for medical vs. recreational users demonstrated that medical users reported more depressed mood and more somatic complaints than recreational users, suggesting that medical conditions clearly contribute to depression scores and should be considered in studies of marijuana and depression. These data suggest that adults apparently do not increase their risk for depression by using marijuana.”

In heavy users seeking treatment, Arendt et al[xxi] reported “Cannabis users had significantly raised levels of depression (p < 0.001) and personality disorders (p < 0.0001) compared with users of other drugs” Arendt et al[xxii], studying cannabis-dependent subjects with depression, reported “While under the influence of cannabis, they more often experienced depression, sadness, anxiety and paranoia, and they were less likely to report happiness or euphoria… Subjects with prior depression do not use cannabis as a mean of self-medication. They are more likely to experience specific increases of adverse symptoms while under the influence of cannabis, and are less likely to experience specific symptom relief.”

Poly-drug users

Comparing relationships between gender, cannabis and MDMA use on depression, Durdle et al[xxiii] reported “Those with lifetime major depression were found, however, to have higher rates of lifetime cannabis use disorder (adjusted OR = 2.40). A logistic regression indicated that lifetime cannabis use disorder, but not MDMA use, was significantly associated with lifetime Major Depressive Disorder. Stratified analyses suggested that for males, neither drug use variable was associated with major depression. For females, a lifetime cannabis use disorder (adjusted OR = 4.99), but not MDMA use, was associated with lifetime Major Depressive Disorder.”

Co-Morbidity

Schizophrenia: In schizophrenia patients, Hambrecht & Hafner[xxv] identified three subtypes of patient in relation to cannabis use: “Group 1 might suffer from the chronic deteriorating influence of cannabis reducing the vulnerability threshold and/or coping resources. Group 2 consists of individuals which are already vulnerable to schizophrenia. Cannabis misuse then is the (dopaminergic) stress factor precipitating the onset of psychosis. Group 3 uses cannabis for self-medication against (or for coping with) symptoms of schizophrenia, particularly negative and depressive symptoms. These patients probably learn to counterbalance a hypodopaminergic prefrontal state by the dopaminergic effects of cannabis.”

Psychosis: Degenhardt et al[xxvi] studying young adults with psychotic disorders reported “Cannabis use predicted a small but statistically significant increase in symptoms of psychosis, but not depression, after controlling for other differences between cannabis users and non-users. Symptoms of depression and psychosis did not predict cannabis use.” Hall & Degenhardt[xxvii] reported “Adolescent cannabis dependence is correlated with an increased risk of using other illicit drugs, symptoms of depression, and symptoms of psychosis.” In a study investigating reasons for cannabis use among patients with psychosis, Schofield et al[xxviii] found “symptoms (of) depression were… important motivators of cannabis use”

Bipolar Disorder: In a study of bipolar patients, Baethge et al[xxix] reported “cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression” In a study of patients with bipolar disorder (manic depressive psychosis), Strakowski et al[xxx] found “The duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania.”

General Psychiatric Disorders: In a study of psychiatric patients, Peters et al[xxxi] reported “Recent-onset patients and UHR subjects reported feeling more anxious, depressed and suspicious immediately after cannabis use. Some patients also reported feeling less depressed after cannabis use. Recent-onset patients reported increased visual and acoustic hallucinations, and confusion after cannabis use.” Katz et al[xxxii] found “Cannabis abusers are obviously less depressive (HAM-D): 5.944 +/- 10.291 vs 12.896 +/- 13.946 (P < .0005, t = 3.535). Such differences were observed in the high number of the subscales. Abusers' rates were higher (although not significantly) for paranoid symptoms and general somatic symptoms. Cannabis possibly produces some antidepressive and anxiolytic effect on psychotic and affective inpatients.”

Suicide

Pedersen[xxxiii], in a population study of links between cannabis use and later development of depression or suicidal ideation, found “In early adolescence, no associations with later depression or suicidal behaviours were observed. In the sample's twenties, we observed highly significant associations with suicide ideation and suicide attempts. When adjusting for confounders, the OR was 2.9 (95% CI 1.3-6.1) for later suicide attempts in the group who had used cannabis 11+ times during the past 12 months… exposure to cannabis by itself does not lead to depression but that it may be associated with later suicidal thoughts and attempts.” Chabrol et al[xxxiv] found “an association between suicidal ideation, depressive symptoms and cannabis use in adolescents. Cannabis use appeared to be an independent predictor of suicidal ideation after controlling for depressive symptoms. However, the increment of variance accounted for by cannabis use was small. This suggests that cannabis use contributes to suicidal ideation independently from depressive symptoms, but weakly.”

Raja & Azzoni[xxxv] reported the case of a patient who twice developed suicidal ideation shortly after using cannabis. Studying suicidal behaviour in Trinidadian adolescents, Maharajh & Konings[xxxvi] reported “depressive and psychotic experiences were common findings in adolescent cannabis users with a significant preponderance of depressive experiences (p<0.01). Our findings suggest that there is a convincing relationship between suicidal behaviour and cannabis use, the latter awakening depressive experiences.”

In high-school students, Chabrol et al[xxxvii] reported “Cannabis use was a significant independent predictor of suicidal behaviors after adjustment for depressive and anxious symptoms.” Arendt et al[xxxviii] reported “Depression, suicidal ideation and suicidal behavior are common phenomena among heavy cannabis users predicted from factors related to childhood and parental alcoholism.” Dhossche et al[xxxix] noted “Detection of alcohol, cocaine, or cannabis in about 40% of suicides supports the clinical practice of discouraging consumption of these substances in depressed patients”.

In a study of twins, Lynksey et al[xl] reported “Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD (major depressive disorder) in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs.”

Self-Medication

Aharonovitch et al[xli] postulated “the self-medication hypothesis of substance abuse... that drug abuse is driven by an attempt to alleviate specific psychological distress”. Abraham & Fava[xlii] studying the order of onset of depression and substance abuse in an attempt to resolve the ‘cause or self-medication’ question, reached no conclusions concerning cannabis alone, but noted “Among polydrug-dependent patients, each drug abused followed the onset of depression, except for LSD, which coincided with the onset of depression.”

Grant et al[xliii] in a US population study, commented “cannabis might be used to self-medicate major depression.” Schnelle et al[xliv] found depression to be the most common reason for self-medication in a study of German-speaking medicinal cannabis patients. In an American epidemiological study of cannabis use, dependence and co-morbidity, Grant & Pickering[xlv] concluded “cannabis might be used to self-medicate major depression.”

Controlled Studies

Kotin et al[xlviii], in a double-blind experiment, found no effect on moderate to severe depression from relatively high doses (0.3mg/kg) of THC. Regelson et alia[xlix] reported a number of significant effects in a controlled study of THC in terminal cancer patients, including a reduction in depression, greater emotional stability, more self-reliant/less dependent, less suspiciousness, increased forthrightness, less apprehension, more normal level of control and more tranquil/relaxed, however two patients who discontinued the study reported fear and anxiety, confused thinking and dissociation. The authors commented that such effects would appear to be confined to a susceptible population.

Secora et al[liii] found “cannabis dependent individuals with comorbid depression showed more psychosocial impairment than individuals with cannabis dependence alone. However, contrary to the authors' hypothesis, individuals who were cannabis dependent with comorbid depression showed less cognitive impairment… than individuals with cannabis dependence alone” concluding “additive effects of cannabis dependency and depression may only be limited to psychosocial domains and may not extend to cognitive functioning.”

Women

In adolescent female smokers of tobacco and/or cannabis, Groth & Morrison-Beedy[liv] found “Girls who smoked either substance had higher scores for depression symptoms, alcohol use and disordered eating when compared to nonsmokers. Girls who used both substances were at a higher risk for alcohol use, depression symptoms and disordered eating” Fattore & Fratta[lv] stated “cannabinoids have been shown to exert sex-dependent effects also in other physiological and behavioural aspects, such as… anxiety and depression (more evident in female”

In a study of self-harming behaviours in a predominantly female sample, Baguelin-Pinaud et al[lvi] noted addictive and eating disorders were often associated with deliberate self-harm. In a study of young women at a sexual health clinic, Fernandez et al[lvii] noted “High depressive scores were significantly associated with a history of self-harm, earlier alcohol use and having tried cannabis, but not with sexual risk behaviours.”

Prisoners

Studying cannabis arrestees diverted into treatment programmes by police, Feeney et al[lix] reported “cannabis dependent participants had significantly higher level of caseness across all subscales of somatic concerns, anxiety, social dysfunction and depression. Dependent women registered the highest proportion of psychopathology, particularly anxiety and social dysfunction.” In Greek prisoners, Fotiadou et al[lx] found “Of those who had a previous history of substance misuse, 31.2% fulfilled the criteria for depression”

Genetic Studies

In a genetic study, Monteleone et al[lxi] suggested differences in CB1-receptor sensitivities may be related to susceptibility to depression and other mood disorders. Ehlers et al noted[lxii] “cannabis-use associated symptoms of depression, trouble concentrating and paranoia were all found to be heritable”

Longitudinal Studies

In a 10 year study, Wittchen et al[lxiii] noted “associations of panic-anxiety with CU (cannabis use) and of depressive and bipolar disorders with CU and CUD (cannabis use disorder) were significant after controlling for externalizing disorders.” Bovasso[lxiv], following a large-scale longitudinal survey of depressive patients, considered cannabis use to be a risk factor for depressive symptoms: “In participants with no baseline depressive symptoms, those with a diagnosis of cannabis abuse at baseline were four times more likely than those with no cannabis abuse diagnosis to have depressive symptoms at the follow-up assessment, after adjusting for age, gender, antisocial symptoms, and other baseline covariates. In particular, these participants were more likely to have experienced suicidal ideation and anhedonia during the follow-up period. Among the participants who had no diagnosis of cannabis abuse at baseline, depressive symptoms at baseline failed to significantly predict cannabis abuse at the follow-up assessment.”

In a survey of young Austrialian adults, Degenhardt et al[lxv] concluded “Cannabis use did not appear to be directly related to depression or anxiety when account was taken of other drug use. However, the association between heavier involvement with cannabis use and affective and anxiety disorders has implications for the treatment of persons with problematic cannabis use.” In a longitudinal study in New Zealand, Fergusson et al[lxvi] reported “For the measures of crime, suicidal behaviours and other illicit drug use there was evidence of age related variation in the strength of association with cannabis use, with younger (14-15 years old) users being more affected by regular cannabis use than older (20-21 years old) regular users. However, the association between cannabis use and depression did not vary with age.”

In a prospective study of adults, Van Laar et al[lxvii] noted “any use of cannabis at baseline predicted a modest increase in the risk of a first major depression (odds ratio 1.62; 95% confidence interval 1.06-2.48) and a stronger increase in the risk of a first bipolar disorder (odds ratio 4.98; 95% confidence interval 1.80-13.81). The risk of 'any mood disorder' was elevated for weekly and almost daily users but not for less frequent use patterns. However, dose-response relationships were less clear for major depression and bipolar disorder separately.” In a large prospective study, Hayatbakhsh et al[lxviii] found “those who started using cannabis before age 15 years and used it frequently at 21 years were more likely to report symptoms of (anxiety & depression) in early adulthood (odds ratio 3.4; 95% CI 1.9-6.1). This association was of similar magnitude for those who had only used cannabis and those who reported having used cannabis and other illicit drugs.”

In a study investigating causality, Libby et al[lxix] found “cannabis dependence was significantly more prevalent among those with depression first.” King et al[lxx] reported “depression may predict initiation of licit substance use in early adolescence” In a cohort study of drug use and mental health in young adults, Patton et al[lxxi] concluded “Daily use in young women was associated with an over fivefold increase in the odds of reporting a state of depression and anxiety after adjustment for intercurrent use of other substances (odds ratio 5.6, 95% confidence interval 2.6 to 12). Weekly or more frequent cannabis use in teenagers predicted an approximately twofold increase in risk for later depression and anxiety (1.9, 1.1 to 3.3) after adjustment for potential baseline confounders. In contrast, depression and anxiety in teenagers predicted neither later weekly nor daily cannabis use.”

Therapeutic Studies

Grinspoon considered cannabinoids to be of promise where depression is secondary to some life event (reactive depression) rather than a primary diagnosis, but did not consider general optimism about such treatment to be justified by the state of knowledge in 1977. Grinspoon[lxxii] later considered some patients who fail to respond to traditional antidepressant drugs, or who find the side-effects of these unbearable, to have been helped by illicit marijuana use, quoting 3 case studies all involving long histories of severe clinical depression, all treated unsuccessfully with all types of antidepressive medication, and all now living normally through use of cannabis, twice daily in one case, on re-appearance of symptoms in the others, each attributing the improvement to greater self-insight, a reduction of a negative self-image, and/or a general euphoria arising from cannabis intoxication.

In a study of therapeutic cannabis users, Swift et al[lxxiii] found “long term and regular medical cannabis use was frequently reported for multiple medical conditions including … depression (56%),”, in patients with sickle-cell anaemia Howard et al[lxxiv] reported “The main reasons for use were to reduce pain in 52%, and to induce relaxation or relieve anxiety and depression in 39%.” In a UK medicinal-users survey, Ware et al[lxxv] reported “medicinal cannabis use was reported by patients with chronic pain (25%), multiple sclerosis and depression (22% each),”

El-Alfy et al[lxxvi] reported in mice “Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis” In a radioligand study of CB1 receptor densities, Koethe et al[lxxvii] found “In major depression, CB(1) receptor immunopositive glial cells in the grey matter were decreased.” Vinod & Hungund[lxxviii] suggested the “CB(1) receptor as a potential therapeutic target for the treatment of alcoholism, depression, anxiety and schizophrenia.”

IDMU Survey Data

In the IDMU surveys conducted between 1994 and 1998, respondents were asked to list any health problems or health benefits experienced as a result of cannabis use. Depression was not a symptom specifically reported however amotivation (including laziness, apathy etc) was reported by 133 respondents (4.8%) and was strongly associated with use of depressants or tranquilliers as well as weaker associations with use of hallucinogens, cannabis, alcohol, ecstasy and caffeine, these users gave lower ratings for cannabis. By contrast, 139 respondents (4.9%) reported antidepressant-related health benefits

In our 1999 survey, respondents were asked to rate the severity and frequency of named problems, for depressive symptoms (apathy/amotivation) 54% of respondents reported experiencing symptoms to some degree, of whom half reported regular problems and 7% of users reporting continual problems, for 8% of users the problems were described as ‘severe’ (Table 8).

Reviews

In a 2000 review, Williamson & Evans[lxxxiii] reported “Not all the observed effects can be ascribed to THC, and the other constituents may also modulate its action; for example CBD reduces anxiety induced by THC. A standardised extract of the herb may be therefore be more beneficial in practice and clinical trial protocols have been drawn up to assess this.” and concluded “Patients taking the synthetic derivative nabilone for neurogenic pain actually preferred cannabis herb and reported that it relieved not only pain but the associated depression and anxiety.”

McGuinness[lxxxiv] concluded “Mood and cognitive effects of marijuana include exacerbation of depression and anxiety” Reece[lxxxv] concluded “Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state”, however Ferigolo et al[lxxxvi] concluded that a “causal relationship between dependence on illicit drugs and depression cannot be determined” and Chen & Lim[lxxxvii] noted “Cannabis use has been consistently reported to be associated with the emergence of psychotic symptoms, yet that seems not to be the case for anxiety and depressive disorders”. Costentin[lxxxviii] concluded that THC “develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC, thus leading to a tolerance (desensitization of CB1 receptors) making anxiety and depression to reappear more intensely than originally.” Hill & Gorzalka[lxxxix] found “endocannabinoid deficiency may underlie some of the symptoms of melancholic depression” Nunn et al[xc] reported “Neither anxiety or depression scores were higher in cannabis users...”, and Dumas et al[xci] reported “The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions”. De Irala et al[xcii] concluded “The fact that unreported or subclinical psychological problems might have preceded and precipitated cannabis use is a very unlikely explanation when the cannabis-psychosis outcome link is assessed from different longitudinal studies.”Kalant[xciii] reported “A weak… but significant link between cannabis and depression has been found in various cohort studies, but the nature of the link is not yet clear.”

Degenhardt et al[xciv] reported “Heavy cannabis use and depression are associated and evidence from longitudinal studies suggests that heavy cannabis use may increase depressive symptoms among some users. It is still too early, however, to rule out the hypothesis that the association is due to common social, family and contextual factors that increase risks of both heavy cannabis use and depression.” Grover & Basu[xcv] concluded “Current evidence indicates that there is a clinically significant association between cannabis use disorders and psychotic syndromes, depression, anxiety and possibly mild cognitive impairment. However, the nature of this association is often not clear.” Rey et al[xcvi] concluded “There is growing evidence that early and regular marijuana use is associated with later increases in depression, suicidal behavior, and psychotic illness”

Reviewing studies in 2010, Lubman & Baker[xcvii] concluded “Early and heavy use of cannabis has been associated with the onset of psychosis and depression, while chronic use results in poorer treatment outcomes among those with co-occurring mental disorders.” Sanches & Marques[xcviii] concluded “higher use of cannabis is associated with an increased risk of developing bipolar disorder, and probably, major depression in subjects initially without affective disorder, but was not found increased risk of cannabis use among those initially only with mania or depression.” Diehl et al[xcix] noted “In respect to depression, there is no clear evidence to date that depressive patients use cannabis as a form of self-medication.”

Conclusions – Cannabis & Depression

The relationship between cannabis and endocannabinoids and depressive disorders is complex. Results of individual studies need to be treated with caution as experimenter bias based on attitudes to cannabis can influence authors’ conclusions. In a cluster-analyais study of psychiatrists attitudes to cannabis risks in Switzerland, Zullino et al[c] found “"Prohibitionists" believed that cannabis could induce and trigger all forms of psychiatric disorder, and showed a highly prohibitive attitude… "Causalists" believed that schizophrenia, but not other psychiatric disorders, could be induced and triggered... "Prudent liberals" did not believe that psychiatric disorders could be induced by cannabis, and were generally less prohibitive.”

It is clear that incidence of depression amongst users of cannabis is significantly higher than in the equivalent population of non-users, and that several studies have found correlations between levels or frequencies of cannabis use and symptom severity. However a causal relationship is far from established. There is evidence from animal and brain-imaging studies to suggest the body’s own endocannabinoid system is involved in the regulation of mood and may mediate depression. However THC, the active ingredient in cannabis has been shown to have antidepressant properties, and experimental studies have failed to find consistent evidence of development of depressive symptoms among experimental subjects exposed to cannabis or THC.

There is strong evidence that many depressed patients self-medicate with cannabis, raising the causal question as to whether cannabis use leads to depression, or whether depression leads to cannabis use. Longitudinal studies investigating relevant onset times of depression and cannabis use have produced conflicting results. There is a worrying relationship between cannabis use in adolescence and suicidal ideation or attempts, however again the causality is in question.

There does appear to be a genetic component to susceptibility to depression based on receptor and gene studies, with women more likely to report depressive symptoms or to self-medicate depressive symptoms with cannabis.